Abstract
Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence. Although aspects of this model are controversial, such observations suggest a number of approaches to further enhance the use of morphine as an analgesic.
Keywords: morphine, tolerance, dependence, receptor internalisation, desensitization
CNS & Neurological Disorders - Drug Targets
Title: Opioid Regulation of Mu Receptor Internalisation: Relevance to the Development of Tolerance and Dependence
Volume: 9 Issue: 5
Author(s): Juan F. Lopez-Gimenez and Graeme Milligan
Affiliation:
Keywords: morphine, tolerance, dependence, receptor internalisation, desensitization
Abstract: Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence. Although aspects of this model are controversial, such observations suggest a number of approaches to further enhance the use of morphine as an analgesic.
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Cite this article as:
F. Lopez-Gimenez Juan and Milligan Graeme, Opioid Regulation of Mu Receptor Internalisation: Relevance to the Development of Tolerance and Dependence, CNS & Neurological Disorders - Drug Targets 2010; 9 (5) . https://dx.doi.org/10.2174/187152710793361522
DOI https://dx.doi.org/10.2174/187152710793361522 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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